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Amyloid-beta-induced degeneration of human brain pericytes is dependent on the apolipoprotein E genotype.
[hereditary cerebral hemorrhage with amyloidosis]
Amyloid-
beta
(
A
beta
)
deposition
in
cerebral
vessels
(
cerebral
amyloid
angiopathy
,
CAA
)
is
accompanied
by
degeneration
of
vascular
cells
,
including
pericytes
and
smooth
muscle
cells
.
Previous
studies
indicated
that
specific
A
beta
protein
isoforms
are
toxic
for
cultured
human
brain
pericytes
and
smooth
muscle
cells
.
In
particular
,
A
beta
1
-
40
carrying
the
E
22
Q
mutation
,
as
in
hereditary
cerebral
hemorrhage
with
amyloidosis
of
the
Dutch
type
(
HCHWA-D
)
,
is
toxic
.
We
investigated
the
effects
of
the
A
beta
-binding
protein
apolipoprotein
E
(
ApoE
)
on
the
toxicity
of
A
beta
for
cultured
human
brain
pericytes
.
We
compared
the
toxicity
of
HCHWA-D
A
beta
1
-
40
for
pericyte
cultures
with
different
ApoE
genotypes
,
studied
the
accumulation
of
A
beta
and
ApoE
in
these
different
cell
cultures
,
and
investigated
the
effects
of
exogenous
ApoE
.
Pericyte
cultures
with
an
ApoE
epsilon
2
/
epsilon
3
genotype
were
more
resistant
to
HCHWA-D
A
beta
1
-
40
treatment
than
cultures
with
a
epsilon
3
/
epsilon
3
or
epsilon
3
/
epsilon
4
genotype
.
Cell
death
was
highest
in
cultures
homozygous
for
ApoE
epsilon
4
.
The
extent
to
which
both
A
beta
ApoE
accumulated
at
the
cell
surface
was
parallel
to
the
degree
of
toxicity
.
The
addition
of
purified
ApoE
resulted
in
a
decrease
in
cell
death
.
These
data
suggest
that
ApoE
4
may
direct
A
beta
more
efficiently
than
other
ApoE
isoforms
into
a
pathological
interaction
with
the
HBP
cell
surface
.
The
results
of
this
study
are
in
line
with
the
observations
that
inheritance
of
the
ApoE
epsilon
4
allele
increases
the
risk
of
developing
Alzheimer
's
disease
,
and
that
the
ApoE
epsilon
2
allele
has
a
relatively
protective
effect
.